High dietary methionine plus cholesterol stimulates early athersclerosis and late fibrous cap development which is associated with a decrease in GRP78 positive plaque cells

Hare, David L and Zulli, Anthony
(2009)
High dietary methionine plus cholesterol stimulates early athersclerosis and late fibrous cap development which is associated with a decrease in GRP78 positive plaque cells.
International Journal of Experimental Pathology, 90 (3).
pp. 311-320.
ISSN 1365-2613

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Abstract

The role of homocysteine, or its precursor methionine, in the formation of fibrous
caps and its association with endoplasmic reticulum (ER) stress is unclear. Homocysteine
can stimulate collagen accumulation and upregulate the ER stress chaperone
glucose regulated protein 78 (GRP78). The aim of this study was to determine if
high dietary methionine would increase fibrous caps, and that removal of an atherogenic
diet would decrease the amount of ER stressed cells. New Zealand white rabbits
were fed for 2, 4, or 12 weeks an atherogenic diet [1% methionine + 0.5%
cholesterol (2MC, 4MC or 12MC)]; for 4 or 12 weeks a 0.5% cholesterol diet
(4Ch, 12Ch); and to study plaque regression, an MC diet for 2 or 4 weeks accompanied
by 10 weeks of a normal diet (2MCr, 4MCr). Endothelial function, atherosclerosis
and GRP78 positive cells were studied. Endothelial function was abolished in
4MC and atherosclerosis increased 17-fold (P < 0.05) compared with 4Ch. Fibrous
caps composed 48% of total plaque area in 12MC vs. 10% in 12Ch (P < 0.01), and
12MC expressed less GRP78 plaque cells vs. 12Ch (P < 0.01). Four MCr had less
plaque GRP78 cells than 12MC (P < 0.05) and less endothelial GRP78 cells
(P < 0.01). In addition, GRP78 positive cells were the highest in 4MC, but decreased
in all other groups (P < 0.01). GRP78 positive cells within the fibrous cap inversely
correlated with cap size (r2 = 0.9). These studies suggest that high dietary methionine
could be beneficial for plaque stabilisation, and a normal diet also stabilises plaque
and decreases the number of stressed plaque cells.